The North China Craton (NCC) is one of the oldest cratons in the world. It is important to understand the mechanism of NCC destruction. The lithosphere effective elastic thickness (Te) with its anisotropy can provide new insights into those mechanisms, as the spatial distribution patterns of Te and its anisotropy serve as distinctive indicators of past tectonic processes that are difficult to characterize through conventional approaches. The Te and load ratio (F) around the NCC region are estimated using a joint inversion method that integrated both admittance and coherence techniques. The Te anisotropy is estimated using fan wavelet coherence method. The derived Te and F are used to compute flexural isostatic anomalies (FIA) using the theoretical Bouguer admittance method. We find the Te, F, Te anisotropy, and FIA vary a lot from east to west in the NCC area. The Ordos Basin in the western North China Craton (WNCC) has high Te, low F, and weak Te anisotropy, suggesting that the lithosphere of Ordos Basin have high strength and in a state of stable. The Trans-North China Orogen (TNCO) is located in transition zone of Te, F, Te anisotropy, and FIA, indicating that the TNCO could be the front of collision between Eurasia Plate and western Pacific Plate. The eastern North China Craton (ENCC) lithosphere has been largely modified by the deep tectonic activities due to the subduction of western Pacific Plate.

Rituximab (RTX) is an effective treatment for children with steroid-resistant immune thrombocytopenia (ITP), but reliable biomarkers to predict its response early are lacking. We analysed urine samples from 37 steroid-resistant ITP patients-17 RTX responders (RTX-R) and 20 RTX non-responders (RTX-NR)-along with 40 healthy controls using a discovery-validation proteomics workflow. In the discovery cohort, we identified 78 differential proteins (DPs) before treatment and 67 DPs after treatment using the data-independent acquisition (DIA) approach. The RTX-R group was associated with humoral immunity and complement activation before treatment, while the RTX-NR group showed stronger connections to cellular immunity and glycolysis. The Mfuzz analysis indicated that RTX worked by reducing the B-cell receptor pathway and lipid metabolism while enhancing platelet activation. We validated two proteins (KLK6 and FUBP1) as candidate biomarkers for predicting RTX response through parallel reaction monitoring (PRM) technology, achieving an area under the curve (AUC) of 0.98, with a sensitivity of 1.00 and specificity of 0.85. A monitoring model with HK1, FUBP1, LAIR2, CSTA and RPL12 differentiated RTX-R from RTX-NR after treatment, yielding an AUC of 1.00, sensitivity of 0.92 and specificity of 0.95. Overall, these findings enhance our understanding of RTX mechanisms and support personalized therapy development for ITP.

BACKGROUND:Bacterial meningitis complicated by neurological complications (BMN) is a major cause of poor outcomes and mortality among children with bacterial meningitis. So far, the host-related mechanisms and diagnostic biomarkers of BMN and bacterial meningitis without neurological complications (BM) remain poorly understood and limited. METHODS:We implemented a two-stage cerebrospinal fluid (CSF) quantitative proteomics study involving three groups: children with BMN, BM, and diseases not involving the central nervous system(Ctrl). Initially, in the discovery cohort, data-independent acquisition (DIA) mass spectrometry was used for proteomic profiling on 242 CSF samples (77 BMN, 52 BM, and 113 Ctrl). Differentially expressed proteins (DEPs) were identified among the BMN/Ctrl, BM/Ctrl, and BMN/BM groups, followed by an analysis of their functional enrichment. Next, the parallel reaction monitoring (PRM) method was used to validate the essential DEPs identified during the DIA phase in a validation cohort of 196 subjects (94 BMN, 47 BM, and 55 Ctrl). Subsequently, the validated DEPs were further filtered to construct a PRM-based machine learning model that distinguishes between BMN and BM. RESULTS:A total of 1376 DEPs were identified in BM/Ctrl (757 upregulated, 619 downregulated), 1295 in BMN/Ctrl (745 upregulated, 550 downregulated), and 356 in BMN/BM(60 upregulated, 296 downregulated), respectively. The functional results indicate that the upregulated DEPs were primarily enriched in immunity, inflammation, complement, and phagocytosis in BMN/Ctrl and BM/Ctrl. Immunoglobulin production, phagocytosis, and the classical pathway of complement activation were further upregulated in BMN/BM. The downregulated DEPs are primarily enriched in cell adhesion, nervous system function, and synapses in BMN/Ctrl and BM/Ctrl; some were further enriched in BMN/BM. In addition, some of the innate immunity, translation, signal transduction, nervous system, and redox processes were mainly downregulated in BMN/BM. The PRM successfully verified 22 significant DEPs. Among them, UAB1, MTPN, ARHGDIB, IGHG3, and AMBP could be combined to distinguish BMN from BM, achieving an AUC of 0.998 in the training set and 0.824 in the validation set. CONCLUSIONS:This study identified distinct CSF protein expression profiles in children with BMN, BM, and Ctrl, potentially enhancing our understanding of the molecular mechanisms underlying bacterial meningitis. These protein signatures help us distinguish bacterial meningitis from the Ctrl group. Furthermore, selected biomarkers could support the differentiation between BMN and BM.

Methylmalonic acidemia (MMA) is the most common organic acidemia in childhood. Brain injury represents the most common clinical manifestation among MMA patients and is often associated with a poor prognosis. Currently, the mechanisms of MMA with brain injury are unclear, and there are no reliable biomarkers available for diagnosing MMA with brain injury. Consequently, a proteomic analysis was performed on the serum from 40 patients with MMA with brain injury (MBI), 15 MMA without brain injury (MNBI), 15 hyperhomocysteinemia patients (HHCY), and 25 healthy controls (CTRL). The differentially expressed proteins were analyzed by bioinformatics, and then the potential biomarkers were validated by the enzyme-linked immunosorbent assays in another independent cohort. The results showed that a total of 503 proteins were identified in the serum samples, of which 49 differentially expressed proteins were identified in the MBI and MNBI groups. Two key molecules were identified as candidate molecules for further validation. The combination of ACE and MMP9 might be a biomarker panel for MMA with brain injury (AUC 0.847, sensitivity 0.750, specificity 0.867). The down-regulation of immune response and up-regulation of inflammatory response were mainly enriched in MMA brain injury patients. Our research indicated that dysregulation of immune response and neuroinflammation might be potential mechanisms of MMA with brain injury. In addition, it provided a candidate biomarker panel for early diagnosing MMA with brain injury, facilitating early intervention and prognosis improvement.

BackgroundAbdominal Henoch - Schönlein purpura (AHSP), being the most prevalent form of Henoch - Schönlein purpura, has a significant impact on the short - term prognosis of the disease and often involves the kidneys, leading to renal complications that affect children's long - term prognosis. However, the existing early assessment criteria for AHSP and its renal complications are inadequate. The urinary proteome may offer valuable insights.ObjectiveTo confirm the significance of urinary proteomics in the early detection of AHSP and its renal complications in children.MethodsThe urinary proteome of AHSP patients (with and without renal involvement) was compared with that of healthy controls using liquid chromatography - tandem mass spectrometry (LC - MS/MS) in data - independent acquisition (DIA) mode. Differentially expressed proteins were analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Mfuzz was employed to analyze the expression levels of proteins related to disease onset and progression. The STRING database was used for protein - protein interaction analysis of relevant biological pathways. Selected differential proteins were verified using parallel reaction monitoring (PRM).ResultsA total of 441 dysregulated differentially expressed proteins (DEPs) were associated with the pathogenesis of AHSP, mainly related to cell adhesion, signal transduction or regulation, and reactions or pathways mediated by inflammatory cells or factors, and predominantly enriched in the lysosomal pathway. A total of 275 DEPs related to renal complications of AHSP were mainly associated with immune processes mediated by immunoglobulins, predominantly enriched in the regulatory pathways of the actin cytoskeleton. Time series clustering analysis identified 10 discrete clusters; three upregulated and two downregulated clusters were chosen to form respective panels. These panels involved various biological processes such as immune and inflammatory processes, lipid metabolism, glycosylation, coagulation, oxidative detoxification processes, and the Wnt signaling pathway, with several important biological pathways being enriched. Protein - protein interaction analysis of key pathways revealed three distinct MCODE networks, mainly involving proteins related to immunity, coagulation, collagen, and integrins. In the validation phase, at least eight urinary proteins useful for diagnosing AHSP or its renal complications were identified, demonstrating good diagnostic performance.ConclusionThis study offers novel perspectives on the pathogenesis of AHSP and its renal complications in children, and the related proteins may serve as potential biomarkers for diagnosing AHSP and identifying the onset of renal damage. The findings of this study emphasize the importance of urinary proteomics in understanding the disease mechanisms and provide a basis for further research on early diagnosis and treatment.

BACKGROUND:Streptococcus pneumoniae meningitis (SPM) is a critical pediatric infection with a high mortality rate. This study aimed to investigate changes in the cerebrospinal fluid (CSF) proteome in SPM patients and identify biomarkers for SPM diagnosis and treatment monitoring. RESEARCH DESIGN AND METHODS:Here, we retrospectively collected and evaluated CSF proteomes of 47 SPM and 116 non-CNS-infected patients (Control), including longitudinal samples from 11 SPM patients. Candidate biomarkers were validated by parallel reaction monitoring (PRM) in 146 samples (36 longitudinal/12 SPM, 110 Control) and evaluated via receiver operating characteristic (ROC) analysis. RESULTS:We identified 648 differentially expressed proteins (DEPs) associated with complement activation and oxidative stress. SPM patients with abnormal CSF white blood cells (SPMAN) exhibited dysregulation in coagulation and fibrinolysis, while those with normal counts (SPMN) displayed redox homeostasis alterations. The ELANE and H4C1 panel achieved a superior diagnostic accuracy (AUC = 0.967), and the combination of IGKV1-17, IGKC, and IGKV4-1 effectively tracked therapy response (AUC = 0.872). CONCLUSION:This study establishes CSF proteomic signatures of pediatric SPM, providing dual-purpose biomarker panels for clinical diagnosis and treatment monitoring, with implications for targeted interventions.

Abstract Objectives To compare the risk of acute kidney injury (AKI) between hospitalized children who received intravenous contrast media for imaging examinations and those who did not. Methods This retrospective cohort study enrolled patients aged 0–18 years with serum creatinine levels before and after imaging examinations from 2015 to 2020 at Beijing Children’s Hospital. Participants were classified into an exposure group or a control group. Log-binomial regression analysis was used to estimate the adjusted risk ratio (aRR) value for the association between exposure to contrast media and consequential AKI. After which, inverse probability treatment weighting was used to reduce systematic differences in baseline characteristics among the groups. Moreover, subgroup and sensitivity analyses were performed. Finally, multivariate logistic regression analysis was performed to identify risk factors for pediatric AKI. Results In total, 3061 pediatric patients were included in the analyses (median age, 4.5 [IQR, 1.3–8.9] years, 1760 males). According the KDIGO definition of AKI, the incidence of AKI in the exposure group, and the control group were 7.4% and 6.5%, respectively; furthermore, the aRR was 1.35 (95% CI: 1.31–1.39). In patients underwent CT, the risk of AKI in the exposure group of contrast media increased compared with the control group and the aRR was 1.39 (95% CI: 1.09–1.78). However, it is not observed in patients underwent MRI (aRR: 1.36; 95% CI: 0.96–1.95). According to our subgroup analysis of pediatric patients aged ≥ 2 years (aRR: 1.38; 95% CI: 1.05–1.82) and sensitivity analysis (aRR: 1.32, 95% CI: 1.08–1.61), the risk of AKI in the exposure group was greater than that in the control group. An increased risk to exposure to contrast media was seen in females (aRR: 1.41, 95% CI: 1.05–1.89) rather than males (aRR: 1.30, 95% CI: 0.99–1.70). According to the multivariate logistic regression analyses, the baseline eGFR (OR: 1.02; 95% CI: 1.01–1.03) and comorbidities (OR: 2.97; 95% CI: 1.89–4.65) were risk factors, while age (OR: 0.87; 95% CI: 0.84–0.91) was a protective factor against AKI. Conclusion The evidence from the present study suggested that the increased risk of AKI in hospitalized children induced by intravascular contrast should not be ignored.

Given the spatial resolution of ~300 km in Gravity Recovery and Climate Experiment (GRACE) measurements, accurately quantifying mass variations at smaller scales proves challenging. Here, we present a high-resolution time-variable gravity field model of continental North China. This model, denoted as IGP-NorthChina2022TG, contains 15 gravity field solutions determined using an innovative approach that relies on terrestrial gravity measurements and Slepian basis functions. IGP-NorthChina2022TG provides degree 150 gravity changes (spatial resolution of ~120 km) on a semi-annual basis from September 2009 to September 2016, in contrast to the monthly degree 60 GRACE solutions. Despite their different temporal resolutions, the good agreement between GRACE and the ground-based results up to degree 60 confirms the robustness and reliability of the proposed method and favors the combination of these two types of measurements. The gravity changes with much finer spatial resolution from IGP-NorthChina2022TG could complement GRACE solutions for sub-regional scale investigations in North China.

Land surface water is a key part in the global ecosystem balance and hydrological cycle. Remote sensing has become an effective tool for its spatio-temporal monitoring. However, remote sensing results exemplified in so-called water indices are subject to several limitations. This paper proposes a new and effective water index called the Sentinel Multi-Band Water Index (SMBWI) to extract water bodies in complex environments from Sentinel-2 satellite imagery. Individual tests explore the effectiveness of the SMBWI in eliminating interference of various special interfering cover features. The Iterative Self-Organizing Data Analysis Technique Algorithm (ISODATA) method and confusion matrix along with the derived accuracy evaluation indicators are used to provide a threshold reference when extracting water bodies and evaluate the accuracy of the water body extraction results, respectively. The SMBWI and eight other commonly used water indices are qualitatively and quantitatively compared through vision and accuracy evaluation indicators, respectively. Here, the SMBWI is proven to be the most effective at suppressing interference of buildings and their shadows, cultivated lands, vegetation, clouds and their shadows, alpine terrain with bare ground and glaciers when extracting water bodies. The overall accuracy in all tests was consistently greater than 96.5%. The SMBWI is proven to have a high ability to identify mixed pixels of water and non-water, with the lowest total error among nine water indices. Most notably, better results are obtained when extracting water bodies under interfering environments of cover features. Therefore, we propose that our novel and robust water index, the SMBWI, is ready to be used for mapping land surface water with high accuracy.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

The MS 6.9 Menyuan earthquake occurred in the northeastern Tibetan Plateau on 8 January 2022. High-precision absolute gravity observations provide a unique perspective on seismotectonic feature of strong continental earthquakes. An obvious and coincident gravity increase about 5 years before the Menyuan earthquake with the rate up to 3.94 mu Gal/yr is observed at four absolute gravity stations within 350 km away from the epicenter. These four stations have been carried out repeat gravity observations by the Crustal Movement Observation Network of China (CMONOC) for more than a decade. The observed gravity changes could not be reasonably explained by the land water storage change nor crustal vertical deformation and thus might be related to the processes in the crust. A disc-shaped equivalent source region with a radius of 175 km is then modeled, based on the residual gravity rates. We find that the seismicity increases gradually in the modeled source region from about 2017 to 2021, similar to the pattern of absolute gravity change. Furthermore, the spatiotemporal distri-bution of epicenters is consistent with the fluids diffusion model, indicating that this could be related to the redistribution of deep fluid mass. With consideration of the near-surface processes, regional crustal structure, and seismicity, multiple lines of evidence consistently refer to the presence of deep fluids migration before the Menyuan earthquake. Our results suggest that high-precision absolute gravimetry can be used to monitor crustal fluid environment and determine mass changes in the source regions of potential large earthquakes.

Background Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma with poor prognosis in children. The 5-year survival rate for early RMS has improved, whereas it remains unsatisfactory for advanced patients. Urine can rapidly reflect changes in the body and identify low-abundance proteins. Early screening of tumor markers through urine in RMS allows for earlier treatment, which is associated with better outcomes. Methods RMS patients under 18 years old, including those newly diagnosed and after surgery, were enrolled. Urine samples were collected at the time points of admission and after four cycles of chemotherapy during follow-up. Then, a two-stage workflow was established. (1) In the discovery stage, differential proteins (DPs) were initially identified in 43 RMS patients and 12 healthy controls (HCs) using a data-independent acquisition method. (2) In the verification stage, DPs were further verified as biomarkers in 54 RMS patients and 25 HCs using parallel reaction monitoring analysis. Furthermore, a receiver operating characteristic (ROC) curve was used to construct the protein panels for the diagnosis of RMS. Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA) software were used to perform bioinformatics analysis. Results A total of 251 proteins were significantly altered in the discovery stage, most of which were enriched in the head, neck and urogenital tract, consistent with the most common sites of RMS. The most overrepresented biological processes from GO analysis included immunity, inflammation, tumor invasion and neuronal damage. Pathways engaging the identified proteins revealed 33 common pathways, including WNT/β-catenin signaling and PI3K/AKT signaling. Finally, 39 proteins were confirmed as urinary biomarkers for RMS, and a diagnostic panel composed of 5 candidate proteins (EPS8L2, SPARC, HLA-DRB1, ACAN, and CILP) was constructed for the early screening of RMS (AUC: 0.79, 95%CI = 0.66 ~ 0.92). Conclusions These findings provide novel biomarkers in urine that are easy to translate into clinical diagnosis of RMS and illustrate the value of global and targeted urine proteomics to identify and qualify candidate biomarkers for noninvasive molecular diagnosis.

The Tibetan Plateau (TP) has the largest number of high-altitude glaciers on Earth. As a source of major rivers in Asia, this region provides fresh water to more than one billion people. Any terrestrial water storage (TWS) changes there have major societal effects in large parts of the continent. Due to the recent acceleration in global warming, part of the water environment in TP has become drastically unbalanced, with an increased risk of water disasters. We quantified secular and monthly glacier-mass-balance and TWS changes in water basins from April 2002 to December 2021 through the Gravity Recovery and Climate Experiment and its Follow-on satellite mission (GRACE/GRACE-FO). Adequate data postprocessing with destriping filters and gap filling and two regularization methods implemented in the spectral and space domain were applied. The largest glacier-mass losses were found in the Nyainqentanglha Mountains and Eastern Himalayas, with rates of −4.92 ± 1.38 Gt a−1 and −4.34 ± 1.48 Gt a−1, respectively. The Tien Shan region showed strong losses in its eastern and central parts. Furthermore, we found small glacier-mass increases in the Karakoram and West Kunlun. Most of the glacier mass change can be explained by snowfall changes and, in some areas, by summer rainfall created by the Indian monsoon. Major water basins in the north and south of the TP exhibited partly significant negative TWS changes. In turn, the endorheic region and the Qaidam basin in the TP, as well as the near Three Rivers source region, showed distinctly positive TWS signals related to net precipitation increase. However, the Salween River source region and the Yarlung Zangbo River basin showed decreasing trends. We suggest that our new and improved TWS-change results can be used for the maintenance of water resources and the prevention of water disasters not only in the TP, but also in surrounding Asian countries. They may also help in global change studies.

Gravity field is the most basic physical field generated by the material properties of the Earth system. It reflects thespatial distribution, movement and change of materials determined by the interaction and dynamic process inside the Earth. Over the years, a variety of technical means have been used to detect the Earth' s gravity field and supported numerous studies on the global change, resource detection, geological structure movement, water resources change and other related fields of research. Here is part of the progress in surface and marine gravimetry obtained by Chinese geodesy scientists from 2019 to 2023 from the following aspects, including: ① Continuous gravity network in Chinese mainland; ② Application of superconducting gravity measurement;③ Network adjustment for continental-scale gravity survey campaign and data quality control; ④ Regional time-variable gravity field and its application;⑤ Research progress on novel technologies for gravity inversion;⑥ Research progress on marine gravity field determination;⑦ Application research on marine gravity field.

As one of the traditional local operas in China, Gan opera has a unique cultural connotation and aesthetic style, and its costumes are even more distinctive. The costumes of Gan opera are beautifully styled and colourful, reflecting the traditional aesthetics of ancient China. In the costumes, attention is paid to the expression of different characters' identities and personalities, for example, the costumes of characters such as emperors, officials and people are all different. At the same time, Gan opera costumes also pay attention to colour matching, focusing on shades and clearness, and emphasising the use of colour to express the characteristics and characters of different characters. The ornamentation of Gan opera costumes is also very rich, often embellished with patterns of flowers and birds, dragons and phoenixes, and clouds, which are deeply symbolic and meaningful. Gan opera costumes are also very elaborate in terms of detailing, such as embroidery, trimming and cutting, all of which have unique techniques and characteristics. In short, Gan opera costumes are an important part of traditional Chinese culture, embodying the essence of traditional Chinese aesthetics and having high artistic value and cultural significance. The aim of this article is to explore the Chinese aesthetic characteristics of traditional costumes of Gan opera, with a view to providing reference value for relevant researchers.

Aim: To profile the plasma proteomics and metabolomics of patients with renal cysts, sporadic angiomyolipoma (S-AML) and tuberous sclerosis complex related angiomyolipoma (TSC-RAML) before and after everolimus treatment, and to find potential diagnostic and prognostic biomarkers as well as reveal the underlying mechanism of TSC tumorigenesis. Materials and Methods: We retrospectively measured the plasma proteins and metabolites from November 2016 to November 2017 in a cohort of pre-treatment and post-treatment TSC-RAML patients and compared them with renal cyst and S-AML patients by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The tumor reduction rates of TSC-RAML were assessed and correlated with the plasma protein and metabolite levels. In addition, functional analysis based on differentially expressed molecules was performed to reveal the underlying mechanisms. Results: Eighty-five patients with one hundred and ten plasma samples were enrolled in our study. Multiple proteins and metabolites, such as pre-melanosome protein (PMEL) and S-adenosylmethionine (SAM), demonstrated both diagnostic and prognostic effects. Functional analysis revealed many dysregulated pathways, including angiogenesis synthesis, smooth muscle proliferation and migration, amino acid metabolism and glycerophospholipid metabolism. Conclusion: The plasma proteomics and metabolomics pattern of TSC-RAML was clearly different from that of other renal tumors, and the differentially expressed plasma molecules could be used as prognostic and diagnostic biomarkers. The dysregulated pathways, such as angiogenesis and amino acid metabolism, may shed new light on the treatment of TSC-RAML.

目的:调查儿科哮喘药物配备和临床应用现状，探讨国家基本药物目录（NEML）和国家医保药品目录（NDRL）内药物应用于儿科人群的合理性。方法:本研究于2020年8-9月对来自全国46家医疗机构的245名临床药师进行问卷调查，收集基本信息、哮喘药物使用情况、哮喘药物评价情况、哮喘相关药学服务等资料，采用描述性方法进行统计分析。结果:46家医疗机构共配置抗炎平喘药物67种，最常配置及使用的药物分别为吸入用布地奈德混悬液、盐酸肾上腺素注射液、醋酸泼尼松片、孟鲁司特咀嚼片和注射用甲泼尼龙琥珀酸钠。其中，10种常用药物存在超说明书用药、剂型不适宜等临床用药问题。在药物评价方面，基于儿童用药特殊性，超过5%儿科药师建议氨茶碱（片剂）和茶碱（缓释片）从NEML删除。超过5%儿科药师建议班布特罗（口服常释剂型）、倍氯米松（吸入剂）、氨茶碱（口服常释剂型）从NDRL中的甲类调整为乙类或删除。此外，超过30%儿科药师建议7种药物调整为医保甲类，分别为孟鲁司特（咀嚼片）、孟鲁司特（颗粒剂）、沙美特罗替卡松（吸入剂）、布地奈德（吸入剂）、布地奈德福莫特罗（吸入剂）、孟鲁司特（口服常释剂型）和丙卡特罗（口服液体剂）。在药学服务方面，超95%调查对象所在医疗机构已开展哮喘相关用药指导，但仅54.01%哮喘相关用药指导主要人员为儿科药师。结论:本研究从一线药师角度对NEML和NDRL在儿科人群应用的合理性进行评价，为下一步建立我国儿童基本药物目录提供参考。同时，儿科药师还应加强处方前置审核、减少超说明书用药，大力开展药学服务，从而提高哮喘用药知识知晓度，降低患儿哮喘发作率。

The clinical comprehensive evaluation of Chinese patent medicine is an important direction in the evaluation of traditional Chinese medicine(TCM), which positively promotes the development of TCM industry. The evaluation system of Chinese patent medicine is helpful to comprehensively evaluate the clinical value of different Chinese patent medicine in the same category, different dosage forms, and specifications, from different manufacturers on the basis of evidence and value. The establishment of a scientific and reasonable comprehensive evaluation index system for Chinese patent medicine is an important prerequisite to ensure clinical value. However, there has been neither a recognized systematic review on the clinical comprehensive evaluation of Chinese patent medicine nor a methodological system used for reference. The evidence and value: impact on decision-making(EVIDEM), developed by the international research team, is used to evaluate the comprehensive value of medical interventions. EVIDEM provides a methodological tool for scientific decision-making to evaluate evidence and value for health technologies on the basis of the multi-criteria decision analysis(MCDA) model and health technology assessment(HTA). Based on the ongoing EVIDEM research, the present study put forward that EVIDEM-based clinical comprehensive evaluation of Chinese patent medicine consisted of four aspects, seven modules, and ten steps, which is expected to references and practical experience for the follow-up comprehensive evaluation of Chinese patent medicine in the TCM field.

我国儿童用药现存问题突出,表现为临床适宜剂型规格少、超说明书用药、经验性用药等.药品评价通过进行多维度的证据评估来判断药品的临床价值,为解决和改善当前儿童临床用药问题提供了新方法.近年来,真实世界研究在儿童用药评价的重要性被广泛认知,各国重视真实世界证据和真实世界数据在医疗卫生决策中的重要作用.该文就当前真实世界药物评价在儿童用药决策中应用的机遇与挑战进行分析,为推进真实世界药物评价进一步开展及促进儿童临床合理用药提供参考.

Statin-associated muscle symptoms (SAMS) are the main side effects of statins. Currently, there are no effective biomarkers for accurate clinical diagnosis. Urine is not subject to homeostatic control and therefore accumulates early changes, making it an ideal biomarker source. We therefore examined urine proteome changes associated with SAMS. Here, we established a SAMS rat model by intragastric intubation with simvastatin (80 mg/kg). Biochemical analyses and hematoxylin and eosin staining were used to evaluate the degree of muscle injury. The urine proteome on days 3, 6, 9 and 14 was profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Differential proteins on day 14 of SAMS were mainly associated with glycolysis/gluconeogenesis, pyruvate metabolism, metabolism of reactive oxygen species and apoptosis, which were associated with the pathological mechanism of SAMS. Among the 14 differential proteins on day 3, Fibrinogen gamma chain (FIBG), Osteopontin (OSTP) and C-reactive protein (CRP) were associated with muscle damage, while EH domain-containing protein 1(EHD1), Cubilin (CUBN) and Fibronectin (FINC) were associated with the pathogenic mechanisms of SAMS. Our preliminary results indicated that the urine proteome can reflect early changes in the SAMS rat model, providing the potential for monitoring drug side effects in future clinical research. SIGNIFICANCE: This study demonstrate that the early muscle damage caused by simvastatin can be reflected in urinary proteins. The urine proteome also has the potential to reflect the pharmacology and toxicology of drugs in future clinical research.